̽��ֱ�� of Cambridge - organ

Lab-grown ‘mini-bile ducts’ used to repair human livers in regenerative medicine first

cjb250 — Thu, 18 Feb 2021 19:00:42 +0000

̽��ֱ��research paves the way for cell therapies to treat liver disease – in other words, growing ‘mini-bile ducts’ in the lab as replacement parts that can be used to restore a patient’s own liver to health – or to repair damaged organ donor livers, so that they can still be used for transplantation.

Bile ducts act as the liver’s waste disposal system, and malfunctioning bile ducts are behind a third of adult and 70 per cent of children’s liver transplantations, with no alternative treatments. There is currently a shortage of liver donors: according to the NHS, the average waiting time for a liver transplant in the UK is 135 days for adults and 73 days for children. This means that only a limited number of patients can benefit from this therapy.

Approaches to increase organ availability or provide an alternative to whole organ transplantation are urgently needed. Cell-based therapies could provide an advantageous alternative. However, the development of these new therapies is often impaired and delayed by the lack of an appropriate model to test their safety and efficacy in humans before embarking in clinical trials.

Now, in a study published today in Science, scientists at the ̽��ֱ�� of Cambridge have developed a new approach that takes advantage of a recent ‘perfusion system’ that can be used to maintain donated organs outside the body. Using this technology, they demonstrated for the first time that it is possible to transplant biliary cells grown in the lab known as cholangiocytes into damaged human livers to repair them. As proof-of-principle for their method, they repaired livers deemed unsuitable for transplantation due to bile duct damage. This approach could be applied to a diversity of organs and diseases to accelerate the clinical application of cell-based therapy.

“Given the chronic shortage of donor organs, it’s important to look at ways of repairing damaged organs, or even provide alternatives to organ transplantation,” said Dr Fotios Sampaziotis from the Wellcome-MRC Cambridge Stem Cell Institute. “We’ve been using organoids for several years now to understand biology and disease or their regeneration capacity in small animals, but we have always hoped to be able to use them to repair human damaged tissue. Ours is the first study to show, in principle, that this should be possible.”

Bile duct diseases affect only certain ducts while sparing others. This is important because in disease, the ducts in need of repair are often fully destroyed and cholangiocytes may be harvested successfully only from spared ducts.

Using the techniques of single-cell RNA sequencing and organoid culture, the researchers discovered that, although duct cells differ, biliary cells from the gallbladder, which is usually spared by the disease, could be converted to the cells of the bile ducts usually destroyed in disease (intrahepatic ducts) and vice versa using a component of bile known as bile acid. This means that the patient’s own cells from disease-spared areas could be used to repair destroyed ducts.

To test this hypothesis, the researchers grew gallbladder cells as organoids in the lab. Organoids are clusters of cells that can grow and proliferate in culture, taking on a 3D structure that has the same tissue architecture, function and gene expression and genetic functions as the part of the organ being studied. They then grafted these gallbladder organoids into mice and found that they were indeed able to repair damaged ducts, opening up avenues for regenerative medicine applications in the context of diseases affecting the biliary system.

̽��ֱ��team used the technique on human donor livers taking advantage of the perfusion system used by researchers based at Addenbrooke’s Hospital, part of Cambridge ̽��ֱ�� Hospitals NHS Foundation. They injected the gallbladder organoids into the human liver and showed for the first time that the transplanted organoids repaired the organ’s ducts and restored their function. This study therefore confirmed that their cell-based therapy could be used to repair damaged livers.

Professor Ludovic Vallier from the Wellcome-MRC Cambridge Stem Cell Institute, joint senior author, said: “This is the first time that we’ve been able to show that a human liver can be enhanced or repaired using cells grown in the lab. We have further work to do to test the safety and viability of this approach, but hope we will be able to transfer this into the clinic in the coming years.”

Although the researchers anticipate this approach being used to repair a patient’s own liver, they believe it may also offer a potential way of repairing damaged donor livers, making them suitable for transplant.

Mr Kourosh Saeb-Parsy from the Department of Surgery at the ̽��ֱ�� of Cambridge and Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, joint senior author, added: “This is an important step towards allowing us to use organs previously deemed unsuitable for transplantation. In future, it could help reduce the pressure on the transplant waiting list.”

̽��ֱ��research was supported by the European Research Council, the National Institute for Health Research and the Academy of Medical Sciences.

Reference
Sampaziotis, F et al. Cholangiocyte organoids can repair bile ducts after transplantation in human liver. Science; 18 Feb 2021

Scientists have used a technique to grow bile duct organoids – often referred to as ‘mini-organs’ – in the lab and shown that these can be used to repair damaged human livers. This is the first time that the technique has been used on human organs.

Given the chronic shortage of donor organs, it’s important to look at ways of repairing damaged organs, or even provide alternatives to organ transplantation

Fotios Sampaziotis

Can we regenerate damaged organs in the lab?

Dr Fotios Sampaziotis and Dr Teresa Brevini, ̽��ֱ�� of Cambridge

Cholangiocyte organoids reconstruct human bile duct

Cambridge Festival: How organoids help us understand ourselves and treat diseases

13:00-14:00 on Monday 29 March 2021

What are organoids? Where do they come from? And how can organoids be used to help us understand and treat human diseases? Kourosh Saeb-Parsy will be taking part in an event as part of the Cambridge Festival, chaired by Richard Westcott, BBC Science Correspondent.

Booking for the Cambridge Festival opens on Monday 22 February. For details visit the Cambridge Festival website.

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New method developed for ‘up-sizing’ mini organs used in medical research

sc604 — Mon, 08 Feb 2021 17:16:20 +0000

̽��ֱ��researchers, from the ̽��ֱ�� of Cambridge, used their method to culture and grow a ‘mini-airway’, the first time that a tube-shaped organoid has been developed without the need for any external support.

Using a mould made of a specialised polymer, the researchers were able to guide the size and shape of the mini-airway, grown from adult mouse stem cells, and then remove it from the mould when it reached the point where it could support itself.

Whereas the organoids currently used in medical research are at the microscopic scale, the method developed by the Cambridge team could make it possible to grow life-sized versions of organs. Their results are reported in the journal Advanced Science.

Organoids are tiny, three-dimensional cell assemblies that mimic the cell arrangement of fully-grown organs. They can be a useful way to study human biology and how it can go wrong in various diseases, and possibly how to develop personalised or regenerative treatments. However, assembling them into larger organ structures remains a challenge.

Other research teams have experimented with 3D printing techniques to develop larger mini-organs, but these often require an external support structure.

“Mini-organs are very small and highly fragile,” said Dr Yan Yan Shery Huang from Cambridge’s Department of Engineering, who co-led the research. “In order to scale them up, which would increase their usefulness in medical research, we need to find the right conditions to help the cells self-organise.”

Huang and her colleagues have proposed a new organoid engineering approach called Multi-Organoid Patterning and Fusion (MOrPF) to grow a miniature version of a mouse airway using stem cells. Using this technique, the scientists achieved faster assembly of organoids into airway tubes with uninterrupted passageways. ̽��ֱ��mini-airways grown using the MOrPF technique showed potential for scaling up to match living organ structures in size and shape, and retained their shape even in the absence of an external support.

̽��ֱ��MOrPF technique involves several steps. First, a polymer mould – like a miniature version of a cake or jelly mould – is used to shape a cluster of many small organoids. ̽��ֱ��cluster is released from the mould after one day, and then grown for a further two weeks. ̽��ֱ��cluster becomes one single tubular structure, covered by an outer layer of airway cells. ̽��ֱ��moulding process is just long enough for the outer layer of the cells to form an envelope around the entire cluster. During the two weeks of further growth, the inner walls gradually disappear, leading to a hollow tubular structure.

“Gradual maturation of the cells is really important,” said Dr Joo-Hyeon Lee from Cambridge’s Wellcome – MRC Cambridge Stem Cell Institute, who co-led the research. “ ̽��ֱ��cells need to be well-organised before we can release them so that the structures don’t collapse.”

̽��ֱ��organoid cluster can be thought of like soap bubbles, initially packed together to form to the shape of the mould. In order to fuse into a single gigantic bubble from the cluster of compressed bubbles, the inner walls need to be broken down. In the MOrPF process, the fused organoid clusters are released from the mould to grow in floating, scaffold-free conditions, so that the cells forming the inner walls of the fused cluster can be taken out of the cluster. ̽��ֱ��mould can be made into different sizes or shapes, so that the researchers can pre-determine the shape of the finished mini-organ.

“ ̽��ֱ��interesting thing is, if you think about the soap bubbles, the resulting big bubble is always spherical, but the special mechanical properties of the cell membrane of organoids make the resulting fused shape preserve the shape of the mould,” said co-author Professor Eugene Terentjev from Cambridge’s Cavendish Laboratory.

̽��ֱ��team say their method closely approximated the natural process of organ tube formation in some animal species. They are hopeful that their technique will help create biomimetic organs to facilitate medical research.

̽��ֱ��researchers first plan to use their method to build a three-dimensional ‘organ on a chip’, which enables real-time continuous monitoring of cells, and could be used to develop new treatments for disease while reducing the number of animals used in research. Eventually, the technique could also be used with stem cells taken from a patient, in order to develop personalised treatments in future.

̽��ֱ��research was supported in part by the European Research Council, the Wellcome Trust and the Royal Society.

Reference:
Ye Liu et al. ‘Bio-assembling Macro-Scale, Lumenized Airway Tubes of Defined Shape via Multi-Organoid Patterning and Fusion.’ Advanced Science (2021). DOI: 10.1002/advs.202003332

A team of engineers and scientists has developed a method of ‘up-sizing’ organoids: miniature collections of cells which mimic the behaviour of various organs and are promising tools for the study of human biology and disease.

We need to find the right conditions to help the cells in mini-organs self-organise

Yan Yan Shery Huang

Catherine Dabrowska

3D projection of a multi-organoid aggregate

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Wash cycle: making organs fit for transplantation

cjb250 — Wed, 20 Jul 2016 08:25:59 +0000

In a room in the Department of Surgery, a kidney sits inside a chamber connected to tubes and monitors. Solutions and gases are pumping through it and urine is coming out.

In fact, the chamber in itself is not particularly special – it’s an off-the-shelf machine used for cardiac bypass surgery in children: it’s how it has been adapted and the new uses it has found that make it so significant. This machine is able to rejuvenate kidneys deemed not fit for transplant, making them fit and healthy again – and suitable for a recipient.

Professor Andrew Bradley, Head of the Department of Surgery, is quick to point out that it is his team at Addenbrooke’s Hospital, part of Cambridge ̽��ֱ�� Hospitals – particularly Professor Mike Nicholson and Dr Sarah Hosgood – who should take all the credit for this machine, which they refer to as an organ perfusion system.

There is a chronic shortage of suitable organs for transplant and something needs to be done. To help address the problem, in December 2015, Wales became the first country in the UK to make organ donation an ‘opt-out’ system – in other words, doctors would remove the organs from deceased individuals and provide them for use in sick patients unless the individual had explicitly refused consent before their death.

Unfortunately, not every donated organ is suitable for transplant – in the case of kidneys, for example, around 15% are deemed unsuitable. This can be for a variety of reasons, including the age of the donor, their disease history and the length of time the organ has been in cold storage.

“Grading organs is not an exact science – it’s a mixture of factors about the circumstance in which it became available, its storage and how it looks to a trained eye,” says Nicholson. “This isn’t good enough, particularly if it means we’re losing some potentially suitable organs.”

What if there was a way of taking these organs and assessing them systematically? And to take it a step further, could some of them even be rejuvenated? Before coming to Cambridge, Nicholson and Hosgood developed a system while at the ̽��ֱ�� of Leicester that effectively recirculates essential nutrients through the kidney, bringing it back to life.

“We use a combination of red blood cells, a priming solution, nutrients, protective agents and oxygen,” explains Hosgood. “We pump this through the kidney while maintaining a temperature close to our body temperature. It mimics being in the body.”

As the perfusion solution is being circulated, the kidney will begin to function and produce urine. By analysing the contents of this urine and monitoring blood flow, doctors can see how the kidney is performing and whether it might make a viable transplant organ. After just a 60-minute perfusion, the kidneys are resuscitated and are potentially ready for transplantation.

This is no longer just an experiment: since moving to Cambridge, with funding from Kidney Research UK and the National Institute for Health Research, the team has been able to take kidneys rejected from other transplant centres, resuscitate and assess them, then transplant them. In December last year, two individuals on the organ transplant waiting list received the perfect Christmas present courtesy of the Cambridge team: a new kidney.

So far, the team has taken five discarded kidneys and managed to rescue three. “We’re hoping to process another hundred over the next four years,” says Hosgood, who is also working with centres in Newcastle, Edinburgh and at Guy’s Hospital in London, in the hope of replicating their success.

̽��ֱ��current kit, which was not purpose-built for organ perfusion, is bulkier and clumsier than ideal, so the team is currently fundraising to help design a dedicated machine, in collaboration with colleagues from the Department of Engineering. “It’s not very mobile, so we couldn’t use it to help resuscitate organs in transit to other centres.”

Nicholson and Hosgood’s success has spurred on other colleagues. Professor Chris Watson describes himself as “piggybacking” on their work to develop a technique for perfusing livers. ̽��ֱ��situation for liver transplants is even more serious than it is for kidneys: as many as one in five patients on the waiting list will die before a liver becomes available.

So far, his team has taken 12 livers, all but one of which had been rejected by other centres, and successfully resuscitated and transplanted them using a system that builds on the pioneering work of his two colleagues.

“There’s a scene in the Woody Allen film Sleeper where Allen’s character stumbles across a 200-year-old Volkswagen Beetle and manages to start it first time,” he says. “ ̽��ֱ��liver is like that. You take it out of cold storage and expect it to start first time. By first assessing it on our machine, we can be more confident it will work first time.”

In some ways, this has proved more of a challenge than it did for kidneys, he adds. “With kidneys, you can put them in the machine for an hour, resuscitate them and then transplant them. If it doesn’t work immediately, the patient stays on dialysis until it picks up. With a liver, it takes longer to analyse and resuscitate the organ, and if it doesn’t work it’s a disaster for the patient.”

Now that the team has successfully revived and transplanted kidneys and livers, this is by no means the end of the story. There is still much work to be done to further improve the organ – and hence improve the function and prolong survival, says Hosgood.

Once transplanted, organs face a battle with the body’s immune system, which recognises its new occupant as a foreign body. This is one reason why the perfusion system uses only red blood cells, not white – to do so would risk an inflammatory response that could damage the organ.

“Of course, as soon as you transplant the kidney, it will face a similar inflammatory response, but by then it should be in an improved state and able to cope better with what the body throws at it,” she explains. ̽��ֱ��Department is in the process of recruiting 400 patients for a randomised controlled trial to test this technology.

̽��ֱ��perfusion system also enables therapies to be given directly to the kidney. This ensures optimal delivery of the treatment to the targeted organ and avoids any side effects in the patient. One promising avenue of research, in collaboration with Professor Jordan Pober at Yale ̽��ֱ�� (USA), is the use of nanoparticles that target the endothelial cells in the lining of the kidney. These cells play an important role in the inflammatory response after transplantation. “ ̽��ֱ��delivery of nanoparticles in this way may reduce damage to the organ after transplantation,” she adds.

̽��ֱ��shortage of suitable organs is not going away. Not even a UK-wide ‘opt-out’ system is likely to completely eradicate the problem. If anything, the crisis is likely to get worse – the flipside of good news stories such as fewer road traffic fatalities and better medicines that reduce the number of young people dying early. ̽��ֱ��team recognises that the system alone is not the answer, but it brings a new relevance to the old adage “waste not, want not”.

There’s a nationwide shortage of suitable organs for transplanting – but what if some of those organs deemed ‘unsuitable’ could be rejuvenated? Researchers at Addenbrooke’s Hospital have managed just that – and last year gave two patients an unexpected Christmas present.

Grading organs is not an exact science – it’s a mixture of factors about the circumstance in which it became available, its storage and how it looks to a trained eye. This isn’t good enough, particularly if it means we’re losing some potentially suitable organs.

Mike Nicholson

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'Tip Top Stomerij en Wasserette' Linnaeusstraat Amsterdam

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Opinion: Can organs have a sexual identity?

Anonymous — Wed, 24 Feb 2016 15:03:28 +0000

A new study published in Nature suggests that the stem cells that allow our organs to grow “know” their own sexual identity, and this influences how they function. These findings could explain why the prevalence of some diseases, such as certain cancers, differs between the sexes.

Beyond the obvious reproduction-related anatomical differences between males and females, many other organs also show sex specific characteristics, for example in the form of subtle differences in size or in their susceptibility to disease. ̽��ֱ��effect of hormones has been extensively researched, and can explain many of the differences. However, less is known about the potential impact of differences between the cells that created the organs themselves.

̽��ֱ��researchers found important genetic differences at the cellular level and also demonstrated how these differences impact organ growth, independently of circulating hormones. These findings could shed light on why some diseases prevail in men or women.

Regenerating gut cells

To uncover genes that regulate cellular differences between male and female organs, the group, led by Irene Miguel-Aliaga studied intestines of fruit flies. Fruit flies are good experimental systems to investigate gene function and, importantly, they exhibit clear sex-related traits such as body size (females are larger than males) and differences in gut physiology.

̽��ֱ��researchers hypothesised that the differences in size and gut physiology between the sexes might be due to intrinsic genetic differences at the cellular level. By monitoring the degree to which different genes were activated in both sexes, the researchers found that subgroups of genes regulating gut function were activated differently in male and female flies. This suggested that “sex-determination” genes (genes that are active due to sex chromosomes) inside gut cells were affecting organ function.

Gut cells are continuously regenerated by gut stem cells through cell division, in which the parent stem cell typically divides into a stem cell plus a specialised cell which will no longer divide but performs functions of the gut. Several mechanisms adjust stem cell divisions to suit the needs of the tissue (for example, if the gut is damaged, stem cells produce more cells to enable tissue regeneration).

By manipulating genes in the cells to act as more “male” or more “female” the authors demonstrated that sex-determinants endowed “female” intestinal stem cells with better ability to divide. This increased stem cell division resulted in longer and better regenerating female guts compared to male guts. Suppressing this “sex-determination path” specifically in intestinal stem cells of a female fly caused the gut to resemble that of a male fly, and activating it in intestinal stem cells of a male caused its gut to increase in size to that of a normal female fly. Further experiments identified additional links between sex-determinants and cell growth, providing a more complete picture.

Advantages and disadvantages

Higher rates of cell multiplication can have advantages for an organ, in that it can speed up the rate of repair after injury. In the female flies it improves nutrient absorption to accommodate high nutritional demands linked to reproduction. However, higher proliferation also leads to more rapid ageing, and higher vulnerability to tumours. Consistent with this view, the study showed that female flies were more prone to genetically-induced intestinal tumours than males; moreover, the researchers were able to confirm that suppressing the “feminising genes” reduced the ease with which tumours form in the gut of female fruit flies.

̽��ֱ��researchers therefore showed how sex-determining genes in stem cells can control organ function, independently of external hormone influences. This had consequences on organ size and also optimised reproduction in females but came with the risk of increased susceptibility to tumours.

̽��ֱ��findings have broad implications in the way we understand tissue maintenance, disease and ageing. Future work will be needed to investigate if the mechanisms discovered in the fruit flies' intestines are also seen in other tissues, and if they are applicable in mammals. If this is the case (which is considered probable), sex-related differences may affect how cells respond to treatments and so by understanding these differences we might be able to develop more effective therapies.

Golnar Kolahgar, ̽��ֱ��Gurdon Institute, Postdoctoral research associate, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

Inset image: Drosophila immigrans face (John Tann).

Golnar Kolahgar (Gurdon Institute) discusses the suggestion that the stem cells which allow our organs to grow “know” their own sexual identity.

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Framed Embroidery Kidney

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What price a human kidney?

amb206 — Sat, 14 May 2011 08:00:20 +0000

There are desperately poor villages in Asia where few males between the age of 18 and 50 have two kidneys. This is not for some genetic reason; it is because these communities are so impoverished that many men have sold their kidneys in order to raise sums that are unattainable by any other means.

A public talk at Cambridge ̽��ֱ�� on Saturday will draw attention to the extremely difficult and contentious issue of illegal trafficking in human organs – and encourage the audience to think about the complex ethical questions involved. It will also be the inaugural lecture in a research programme focusing on the human organ trade.

̽��ֱ��lecture Illicit Trade in Organs will be given by Dr Frank Madsen, a Danish-born criminologist who is Deputy Director of the Von Hügel Institute at St Edmund’s College, Cambridge. With a distinguished career in the investigation of organised crime, he was head of intelligence at Interpol world headquarters, before working for one of the world’s largest pharmaceutical companies as its director of corporate security.

“You can look at the subject of organ trafficking from many points of view – medical, sociological, anthropological, legal and commercial to mention just a few. And it’s an issue that we need to address from all these angles because only through interdisciplinary analysis will we understand what is a very complicated subject,” says Dr Madsen.

“As a criminologist, my starting point is the mismatch between supply and demand. There are huge waiting lists of people wanting organ transplants – and a scarcity of donated organs. In the UK, for example, in 2009-2010 there were almost 8,000 people on the list for transplants and fewer than 2,700 transplants carried out. In the USA, in April there were more than 120,000 people waiting for organs with 17 people on the list dying every day.”

In spite of more donations, the number of people joining waiting lists is likely increasingly to outstrip the supply of organs. This is explained by a rise in conditions such as diabetes mellitus and high blood pressure. “ ̽��ֱ��gap between supply and demand creates a potential market. Experience shows that the creation of so-called denied demand will inevitably create a lucrative supply chain more often than not dominated by elements that can best be described as organised crime,” says Dr Madsen.

Living organ donors selling their organs – mostly kidneys but also parts of the liver - generally come from poor countries, but not all poor countries generate donors. India, Pakistan, Moldova and Turkey are known to be markets for organs. In the most typical scenario, the donor travels to another country to meet up with the receiver and the surgeon, both of whom typically come from a third country.

This strategy allows the people involved to evade legal restraints and obtain access to acceptable operating theatres. In Sana’a in April 2010 a Jordanian trafficker was arrested as he was preparing to travel to Egypt with seven Yeminis in order to remove their kidneys. ̽��ֱ��donors were exceedingly poor and had been talked into having their organs removed.

“In many instances, those who donate their organs are promised enticing sums of money that are never delivered. This an obvious corollary of forcing any trade underground. Such exploitation should be part of any ethical consideration of the subject but mostly it is not. Another consideration often ignored is the negative consequences for donors of surgery that is not carried out under adequate conditions and without post-operation follow-up,” says Dr Madsen.

We accept the sale of our time and our skills, our energy and our creativity as part of making a living. How we view the sale of part of our physical selves is a very different matter. If we accept organ donation within families, and procedures such as surrogate motherhood, should we be prepared to change our stance on the concept of the “ownership of our body”?

“There is an instinctive repugnance at the thought of selling human body parts. But we are accustomed to going to the market place for what we desire to purchase – and especially so in developed countries. This is called the Lipmann Dichotomy – from Walter Lipmann’s quip that “Americans wish so many things that they at the same time wish to prohibit”,” says Dr Madsen.

Coercion is involved in many cases – and in some instances people have been killed so that their organs can be harvested. In South America homeless people were lured into a hospital with promises of alcohol and their lives were terminated so that their organs could be removed and sold. Those who bought or received these organs may never have known the truth about their source.

Outrage at the human organ trade – and especially its most exploitative aspects - is understandable. However, Dr Madsen urges us to reflect on the issue with honesty: “Our instinct is to condemn illegal trafficking in human organs. But you have to think: if your adored teenage daughter was dying of kidney failure and you had the chance to buy one from someone, who, for example, was very poor and therefore induced to sell a kidney, would you be tempted?"

This week’s talk is an inaugural lecture in a programme to study the human organ trade at the Von Hügel Institute, commencing in October 2011 and led by an international team of researchers. A first step will be an attempt to establish why 41% of families in the UK and 45% in the USA refuse permission for the donation of a deceased relative’s organs. “To change this attitude would not eliminate the human organ trade but it would reduce it considerably,” says Dr Madsen.

Illicit Trade in Organs will take place at Gonville and Caius College, Bateman Auditorium, on Saturday, 14 May 2011, at 4.30 pm. All welcome, no charge.

A public talk at Cambridge ̽��ֱ�� on Saturday will draw attention to the growing illegal trade in human organs and invite discussion of the complex ethical issues involved.

As a criminologist, my starting point is the mismatch between supply and demand. There are huge waiting lists of people wanting organ transplants – and a scarcity of donated organs.

Dr Frank Madsen

5MAGAZINE

Men display their scars after kidney removal

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